Macromolecules 2000, 33, 3731-3738
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Amphiphilic Dendrimers with Both Octyl and Triethylenoxy Methyl Ether Chain Ends Yijun Pan and Warren T. Ford* Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078 Received November 26, 1999 ABSTRACT: Tertiary amine dendrimers with both hydrophilic and hydrophobic chains on every end were synthesized from poly(propyleneimine) dendrimers DAB-dendr-(NH2)n (n ) 8, 32, and 64) using sequential amidations and LiAlH4 reductions. The tertiary amine dendrimers were quaternized completely with methyl iodide and converted to quaternary ammonium chlorides by ion exchange. The quaternary ammonium chloride dendrimers are soluble in both organic solvents and water. 13C NMR spin-lattice relaxation time (T1) measurements show that the conformations of the dendrimers depend on solvent. The quaternary ammonium chloride dendrimers solubilize lipophilic compounds, such as pyrene and Reichardt’s dye, in aqueous solution. The limiting solubility corresponds to one pyrene per dendrimer molecule. The rates of the decarboxylation of 6-nitrobenzisoxazole-3-carboxylic acid in aqueous solutions of the cationic dendrimers were up to 500 times faster than in water alone.
Introduction
Results and Discussion
The term unimolecular micelles was used for amphiphilic dendrimers first by Newkome,1 and many examples have been reported.2-14 Most commonly, amphiphilic dendrimers have carboxylate anions or ammonium cations as end groups and a hydrophobic core. Low molar mass surfactants form micelles in water only when their concentration exceeds the critical micelle concentration (cmc), which depends on the ionic strength and temperature.15 In contrast, dendritic unimolecular micelles retain their colloidal structure regardless of concentration, ionic strength, or temperature. As catalysts, dendritic quaternary ammonium ions are active even at very low concentrations and high ionic strength.16 Amphiphilic dendrimers can solubilize lipophilic compounds in aqueous solutions.1,17-21 These properties may enable applications of dendritic unimolecular micelles in the areas of molecular encapsulation,22 drug delivery, and nanoscopic transport.23 Other amphiphilic dendrimers, different from those resembling conventional micelles, also are attractive for such applications. Dendritic inverse micelles have been made by amidating the primary amine end groups of poly(propyleneimine) dendrimers such as DAB-dendr(NH2)64 with fatty acids24 and by creating alcohol functionality in the core of an aryl benzyl ether dendrimer having tetradecyl chain ends.25 Unimolecular micellar dendrimers have been made by linking dendrons with hydrophobic and hydrophilic end groups to the same core.26 Stimuli responsive hybrid star macromolecular amphiphiles can change conformations as the solvent polarity is varied.27,28 Poly(propyleneimine) dendrimers have been studied extensively and are commercial.14 In this study, we report their modification with both hydrophilic triethylenoxy methyl ether (TEO) and hydrophobic octyl chains at every end and their conversion to quaternary ammonium ion dendrimers by total methylation.29 The quaternary ammonium chloride dendrimers are soluble in both organic solvents and water, solubilize lipophilic compounds in water, and speed the rate of decarboxylation of 6-nitrobenzisoxazole-3-carboxylate ion up to 500 times the rate in water.
Synthesis of Amphiphilic Polyamine Dendrimers. The synthesis of the tertiary amine dendrimer G4(TAn32) (generation 4 tertiary amine with 32 end groups) (5) was achieved in four steps from poly(propyleneimine) dendrimer DAB-dendr-(NH2)32 (1) as shown in Scheme 1. The hydrophobic octyl arms were introduced by an amidation of the surface NH2 groups with octanoyl chloride to give polyamide-terminated dendrimer 2, which was isolated by extraction and purified by chromatography. Amide 2 was reduced to secondary amine 3 by LiAlH4, and the hydrophilic TEO arms were introduced by the corresponding acid chloride to give amide 4. Another LiAlH4 reduction afforded polyamine dendrimer 5. The formation of the amide groups and their subsequent conversions to amine groups were monitored by FT-IR of the amide carbonyl band at 1640-1650 cm-1. Generation 2 dendrimer G2(TAn8) (10) with eight terminal amines and generation 5 dendrimer G5(TAn64) (15) with 64 terminal amines were synthesized from DAB-dendr-(NH2)8 (6) and DAB-dendr-(NH2)64 (11), by the same method. We also converted 6 to a secondary amide by reaction with the acid chloride CH3O(CH2CH2O)2CH2COCl (16). The product was soluble only in water and alcohols and could not be purified by silica chromatography or dissolved into an ether solvent for reduction with LiAlH4. On the other hand, the octyl modified-DABdendr-(NH2)n (n ) 8, 32, and 64) dendrimer amides G2(Am32) (2), G4(Am8) (7), and G5(Am64) (12) were insoluble in 0.1 M aqueous HCl solution. Only the dendrimers with both octyl and TEO chain ends were soluble in both organic solvents and acidic aqueous solutions. The octyl arms must be introduced first because solubilities of the octyl-modified dendrimers in organic solvents facilitate the subsequent LiAlH4 reduction, amidation, and purification. Preparation of Water-Soluble Amphiphilic Polyammonium Dendrimers. The water-insoluble tertiary amine dendrimers 5 and 10 were fully quaternized with excess methyl iodide to give the corresponding polyammonium iodide dendrimers G4(PMI32) (5a) and
10.1021/ma9919864 CCC: $19.00 © 2000 American Chemical Society Published on Web 04/21/2000
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G2(PMI8) (10a). The 1H NMR spectra of 5a and 10a show the absence of the NCH2 and NCH2CH2O peaks of 5 and 10 at 2.40 and 2.62 ppm. The water-soluble polyammonium chloride dendrimers G4(PMCl32) (5b) and G2(PMCl8) (10b) were obtained via ion exchange. The conversion was confirmed by the 1H NMR integration of a newly formed OCH2CH2N+Cl- peak of 5b at 4.32 ppm with respect to the alkyl CH3 peak at 0.84 ppm (OCH2CH2N+Cl-/CH3 2/3 area ratio). All new dendrimer amides and amines were purified using flash chromatography on basic aluminum oxide, and the purity was checked by TLC on silica gel plates pretreated with trimethylamine. The products were characterized by FT-IR, 1H NMR, and 13C NMR analysis, and the products from DAB-dendr-(NH2)8 were also characterized by ESI-MS analysis. Figure 1 shows the 13C NMR spectrum of dendrimer 10. Elemental analysis was obtained only for polyammonium chloride 5b. Even after extensive drying its carbon content was about 4% less than the calculated value. However, analysis showed excellent agreement of experimental C/N and Cl/N mol ratios with the calculated values, which suggests that the impurity causing low C, N, and Cl content was water. The iodine content was
